Bacterial Infections, Obesity
Conditions
Keywords
Bacterial infections, Obesity, pharmacokinetics, clindamycin
Brief summary
The purpose of this study is to better understand how clindamycin works in children who fall in the 85th percentile or higher for body mass index (BMI - a ratio of weight to height). The results of the study will help better understand if children in higher BMI ranges process the medication differently and whether dosing should be adjusted in these children.
Detailed description
This is a prospective, open-label pharmacokinetic and safety study of multiple doses of IV and oral clindamycin in overweight and obese children ages 2 to 17 years of age. The total study duration is expected to be approximately 24 months; each subject will participate in the study for up to 18 days (screening day; treatment days 1-14 \[may be as short as 2 days\] followed by an observation period of 3 days post discontinuation of clindamycin therapy or after day 17 (on day 18) of therapy in those who are treated with more than 14 days of clindamycin).
Interventions
DRUGClindamycin
Schedule includes 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 grams/day. Dosing greater than 2.7g/day will be allowed for children receiving clindamycin as part of clinical care.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The Emmes Company, LLC
Phillip Brian Smith
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* 2 years - \< 18 years of age at the time of first dose of study drug * Suspected or confirmed infection OR receiving IV clindamycin per routine care * Negative serum pregnancy test (if female and has reached menarche) within 24 hours of first dose of study drug and agreement to practice appropriate contraceptive measures, including abstinence, from the time of the initial pregnancy test through the last dose of study drug * BMI ≥ 85th percentile for age and sex, based on Centers for Disease Control (CDC) recommendations * Signed informed consent/Health Insurance Portability and Accountability Act (HIPAA) documents by the parent/legal guardian and assent (if applicable)
Exclusion criteria
* The following apply only to those who are NOT already receiving clindamycin per routine care: 1. History of hypersensitivity or allergic reaction to clindamycin or lincomycin 2. History of C. difficile colitis with previous administration of clindamycin 3. Aspartate aminotransferase (AST) \> 120 units/L 4. Alanine aminotransferase (ALT) \> 210 units/L 5. Total bilirubin \> 3 mg/dL 6. Serum creatinine \> 2 mg/dL 7. Receiving a neuromuscular blocker as part of their therapy * Previous participation in the study * Subject is on prohibited medication or herbal product (see Appendix II) * Subject is receiving extracorporeal life support (ECLS) * Subject is post-cardiac bypass (within 24 hours) * Subject on inotropes/pressors * Any other condition or chronic illness that, in the opinion of the principal investigator, makes participation unadvised or unsafe
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6). | In order to understand the impact of obesity on clindamycin PK, PK data were combined to build a PK model from 3 studies that included both obese and non-obese children: 1) PTN\_Clinda Obese study (clinicaltrials.gov/ct.gov identifier NCT01744730) n = 21; 2) PTN\_POPS study (ct.gov identifier NCT01431326) n = 178; and 3) Staph Trio study (ct.gov identifier NCT01728363) n = 21. The data from the Staph-Trio study were only included for PK modeling and not intended to be compared in the analysis. PK sampling schedule for PTN\_Clinda Obese was: Pre-dose 0 (within 15 minutes prior to IV clindamycin dose), 0.5 (± 5 minutes) after dose was administered, 1-1.5 hours (hrs) after dose, 3-4 hrs after, 5-6 hrs after, and pre-next dose. Samples were collected on multiple days and averaged to arrive at a single value. Comparison of empirical Bayesian Estimates (EBE) for clearance by age cohort are presented below. Sampling schedule details for PTN\_POPS and Staph Trio were comparable. |
| PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples). | In order to understand the impact of obesity on clindamycin PK, PK data were combined to build a PK model from 3 studies that included both obese and non-obese children: 1) PTN\_Clinda Obese study (clinicaltrials.gov/ct.gov identifier NCT01744730) n = 21; 2) PTN\_POPS study (ct.gov identifier NCT01431326) n = 178; and 3) Staph Trio study (ct.gov identifier NCT01728363) n = 21. The data from the Staph-Trio study were only included for PK modeling and not intended to be compared in the analysis. PK sampling schedule for PTN\_Clinda Obese was: Pre-dose 0 (within 15 minutes prior to IV clindamycin dose), 0.5 (± 5 minutes) after dose was administered, 1-1.5 hours (hrs) after dose, 3-4 hrs after, 5-6 hrs after, and pre-next dose. Samples were collected on multiple days and averaged to arrive at a single value. Comparison of EBE for volume of distribution by age cohort are presented below. Sampling schedule details for PTN\_POPS and Staph Trio were comparable. |
Countries
United States
Participant flow
Recruitment details
Eligible participants (inpatients) were recruited in 4 hospitals in the United States. All participants were required to be receiving intravenous (IV) Clindamycin.
Pre-assignment details
Patients between the ages (and inclusive of these ages) of 2 years to 17 years at time of first dose of study medication were screened for all other inclusion and exclusion criteria which includes must have body mass index (BMI) greater than or equal to 85th percentile for age and sex, based on Centers for Disease Control (CDC) recommendations.
Participants by arm
| Arm | Count |
|---|---|
| Clindamycin IV-ages 2 to 11 Years Old (BMI 85-95th Percentile) Clindamycin IV: Children ages 2 to 11 years old with BMI 85th to 95th percentile. Their schedule of IV Clindamycin administration included 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 grams/day. Dosing greater than 2.7g/day was allowed for children receiving clindamycin as part of clinical care. | 4 |
| Clindamycin IV-ages 2 to 11 Years Old (BMI Greater Than 95th) Clindamycin IV: Children ages 2 to 11 years old with BMI greater than 95th percentile. Their schedule of IV Clindamycin administration included 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 grams/day. Dosing greater than 2.7g/day was allowed for children receiving clindamycin as part of clinical care. | 3 |
| Clinidamycin IV-ages 12 to 17 (BMI 85-95th Percentile) Clindamycin IV: Children ages 12 to 17 years old with BMI 85th to 95th percentile. Their schedule of IV Clindamycin administration included 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 grams/day. Dosing greater than 2.7g/day was allowed for children receiving clindamycin as part of clinical care. | 4 |
| Clindamycin IV-ages 12 to 17 (BMI Greater Than 95th) Clindamycin IV: Children ages 12 to 17 years old with BMI greater than 95th percentile. Their schedule of IV Clindamycin administration included 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 grams/day. Dosing greater than 2.7g/day was allowed for children receiving clindamycin as part of clinical care. | 11 |
| Patients Less Than 21 Years of Age (NCT01431326) Standard of care clindamycin administration | 178 |
| Total | 200 |
Baseline characteristics
| Characteristic | Total | Clindamycin IV-ages 2 to 11 Years Old (BMI 85-95th Percentile) | Clindamycin IV-ages 2 to 11 Years Old (BMI Greater Than 95th) | Clinidamycin IV-ages 12 to 17 (BMI 85-95th Percentile) | Clindamycin IV-ages 12 to 17 (BMI Greater Than 95th) | Patients Less Than 21 Years of Age (NCT01431326) |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 200 Participants | 4 Participants | 3 Participants | 4 Participants | 11 Participants | 178 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 7.8 years STANDARD_DEVIATION 6.8 | 9.4 years STANDARD_DEVIATION 2.7 | 10.6 years STANDARD_DEVIATION 1.4 | 14.6 years STANDARD_DEVIATION 1.7 | 14.8 years STANDARD_DEVIATION 1.7 | 7.2 years STANDARD_DEVIATION 6.9 |
| Body Mass Index (BMI) | 85.2 Percentile STANDARD_DEVIATION 24.1 | 90.5 Percentile STANDARD_DEVIATION 3.6 | 97.4 Percentile STANDARD_DEVIATION 1.2 | 91.7 Percentile STANDARD_DEVIATION 3 | 98.3 Percentile STANDARD_DEVIATION 1.3 | 83.1 Percentile STANDARD_DEVIATION 25.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 54 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 142 Participants | 3 Participants | 2 Participants | 3 Participants | 10 Participants | 124 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Gender Female | 78 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 74 Participants |
| Gender Male | 122 Participants | 2 Participants | 3 Participants | 3 Participants | 10 Participants | 104 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 30 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 15 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 13 Participants |
| Race (NIH/OMB) White | 150 Participants | 4 Participants | 2 Participants | 2 Participants | 10 Participants | 132 Participants |
| Region of Enrollment United States | NA participants | 4 participants | 3 participants | 4 participants | 11 participants | NA participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 4 | 0 / 3 | 0 / 4 | 2 / 11 | 0 / 178 |
| serious Total, serious adverse events | 1 / 4 | 0 / 3 | 0 / 4 | 0 / 11 | 0 / 178 |
Outcome results
Primary
Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
In order to understand the impact of obesity on clindamycin PK, PK data were combined to build a PK model from 3 studies that included both obese and non-obese children: 1) PTN\_Clinda Obese study (clinicaltrials.gov/ct.gov identifier NCT01744730) n = 21; 2) PTN\_POPS study (ct.gov identifier NCT01431326) n = 178; and 3) Staph Trio study (ct.gov identifier NCT01728363) n = 21. The data from the Staph-Trio study were only included for PK modeling and not intended to be compared in the analysis. PK sampling schedule for PTN\_Clinda Obese was: Pre-dose 0 (within 15 minutes prior to IV clindamycin dose), 0.5 (± 5 minutes) after dose was administered, 1-1.5 hours (hrs) after dose, 3-4 hrs after, 5-6 hrs after, and pre-next dose. Samples were collected on multiple days and averaged to arrive at a single value. Comparison of empirical Bayesian Estimates (EBE) for clearance by age cohort are presented below. Sampling schedule details for PTN\_POPS and Staph Trio were comparable.
Time frame: After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6).
Population: In order to determine the impact of obesity and the best weight measure for dosing, only children ≥ 2 years of age were compared (PTN\_Clinda obese study n = 21; PTN\_POPS study n = 104; and Staph Trio study n = 0). The PK model suggested dosing should be based on Total Body Weight (TBW) regardless of obesity status.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clindamycin- Ages >2 to 6 Years Old (Non-Obese) | Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 4.2 L/h |
| Clindamycin- Ages >2 to 6 Years Old (Obese) | Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 5.7 L/h |
| Clindamycin- Ages >6 to 12 Years Old (Non-Obese) | Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 12.5 L/h |
| Clindamycin- Ages >6 to 12 Years Old (Obese) | Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 10.7 L/h |
| Clindamycin- Age >12 Years Old (Non-Obese) | Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 14.3 L/h |
| Clindamycin- Age >12 Years Old (Obese) | Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 19.2 L/h |
Primary
Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
In order to understand the impact of obesity on clindamycin PK, PK data were combined to build a PK model from 3 studies that included both obese and non-obese children: 1) PTN\_Clinda Obese study (clinicaltrials.gov/ct.gov identifier NCT01744730) n = 21; 2) PTN\_POPS study (ct.gov identifier NCT01431326) n = 178; and 3) Staph Trio study (ct.gov identifier NCT01728363) n = 21. The data from the Staph-Trio study were only included for PK modeling and not intended to be compared in the analysis. PK sampling schedule for PTN\_Clinda Obese was: Pre-dose 0 (within 15 minutes prior to IV clindamycin dose), 0.5 (± 5 minutes) after dose was administered, 1-1.5 hours (hrs) after dose, 3-4 hrs after, 5-6 hrs after, and pre-next dose. Samples were collected on multiple days and averaged to arrive at a single value. Comparison of EBE for clearance by age cohort normalized to 1 kg of body weight are presented below. Sampling schedule details for PTN\_POPS and Staph Trio were comparable.
Time frame: After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).
Population: In order to determine the impact of obesity and the best weight measure for dosing, only children ≥ 2 years of age were compared (PTN\_Clinda obese study n = 21; PTN\_POPS study n = 104; and Staph Trio study n = 0). The PK model suggested dosing should be based on Total Body Weight (TBW) regardless of obesity status.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clindamycin- Ages >2 to 6 Years Old (Non-Obese) | Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 0.2 L/h/kg |
| Clindamycin- Ages >2 to 6 Years Old (Obese) | Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 0.3 L/h/kg |
| Clindamycin- Ages >6 to 12 Years Old (Non-Obese) | Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 0.3 L/h/kg |
| Clindamycin- Ages >6 to 12 Years Old (Obese) | Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 0.2 L/h/kg |
| Clindamycin- Age >12 Years Old (Non-Obese) | Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 0.2 L/h/kg |
| Clindamycin- Age >12 Years Old (Obese) | Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 0.2 L/h/kg |
Primary
Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
In order to understand the impact of obesity on clindamycin PK, PK data were combined to build a PK model from 3 studies that included both obese and non-obese children: 1) PTN\_Clinda Obese study (clinicaltrials.gov/ct.gov identifier NCT01744730) n = 21; 2) PTN\_POPS study (ct.gov identifier NCT01431326) n = 178; and 3) Staph Trio study (ct.gov identifier NCT01728363) n = 21. The data from the Staph-Trio study were only included for PK modeling and not intended to be compared in the analysis. PK sampling schedule for PTN\_Clinda Obese was: Pre-dose 0 (within 15 minutes prior to IV clindamycin dose), 0.5 (± 5 minutes) after dose was administered, 1-1.5 hours (hrs) after dose, 3-4 hrs after, 5-6 hrs after, and pre-next dose. Samples were collected on multiple days and averaged to arrive at a single value. Comparison of EBE for clearance by age cohort normalized to 70 kg of body weight are presented below. Sampling schedule details for PTN\_POPS and Staph Trio were comparable.
Time frame: After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).
Population: In order to determine the impact of obesity and the best weight measure for dosing, only children ≥ 2 years of age were compared (PTN\_Clinda obese study n = 21; PTN\_POPS study n = 104; and Staph Trio study n = 0). The PK model suggested dosing should be based on Total Body Weight (TBW) regardless of obesity status.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clindamycin- Ages >2 to 6 Years Old (Non-Obese) | Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 10.6 L/h/70 kg |
| Clindamycin- Ages >2 to 6 Years Old (Obese) | Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 14.8 L/h/70 kg |
| Clindamycin- Ages >6 to 12 Years Old (Non-Obese) | Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 20.7 L/h/70 kg |
| Clindamycin- Ages >6 to 12 Years Old (Obese) | Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 14.7 L/h/70 kg |
| Clindamycin- Age >12 Years Old (Non-Obese) | Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 15.8 L/h/70 kg |
| Clindamycin- Age >12 Years Old (Obese) | Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 14 L/h/70 kg |
Primary
PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
In order to understand the impact of obesity on clindamycin PK, PK data were combined to build a PK model from 3 studies that included both obese and non-obese children: 1) PTN\_Clinda Obese study (clinicaltrials.gov/ct.gov identifier NCT01744730) n = 21; 2) PTN\_POPS study (ct.gov identifier NCT01431326) n = 178; and 3) Staph Trio study (ct.gov identifier NCT01728363) n = 21. The data from the Staph-Trio study were only included for PK modeling and not intended to be compared in the analysis. PK sampling schedule for PTN\_Clinda Obese was: Pre-dose 0 (within 15 minutes prior to IV clindamycin dose), 0.5 (± 5 minutes) after dose was administered, 1-1.5 hours (hrs) after dose, 3-4 hrs after, 5-6 hrs after, and pre-next dose. Samples were collected on multiple days and averaged to arrive at a single value. Comparison of EBE for volume of distribution by age cohort are presented below. Sampling schedule details for PTN\_POPS and Staph Trio were comparable.
Time frame: After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).
Population: In order to determine the impact of obesity and the best weight measure for dosing, only children ≥ 2 years of age were compared (PTN\_Clinda obese study n = 21; PTN\_POPS study n = 104; and Staph Trio study n = 0). The PK model suggested dosing should be based on Total Body Weight (TBW) regardless of obesity status.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clindamycin- Ages >2 to 6 Years Old (Non-Obese) | PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 15.3 L |
| Clindamycin- Ages >2 to 6 Years Old (Obese) | PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 17.6 L |
| Clindamycin- Ages >6 to 12 Years Old (Non-Obese) | PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 29.0 L |
| Clindamycin- Ages >6 to 12 Years Old (Obese) | PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 46.9 L |
| Clindamycin- Age >12 Years Old (Non-Obese) | PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 60.1 L |
| Clindamycin- Age >12 Years Old (Obese) | PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 85.8 L |
Primary
PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
In order to understand the impact of obesity on clindamycin PK, PK data were combined to build a PK model from 3 studies that included both obese & non-obese children: 1) PTN\_Clinda Obese study (clinicaltrials.gov/ct.gov identifier NCT01744730) n = 21; 2) PTN\_POPS study (ct.gov identifier NCT01431326) n = 178; and 3) Staph Trio study (ct.gov identifier NCT01728363) n = 21. The data from the Staph-Trio study were only included for PK modeling and not intended to be compared in the analysis. PK sampling schedule for PTN\_Clinda Obese was: Pre-dose 0 (within 15 minutes prior to IV clindamycin dose), 0.5 (± 5 minutes) after dose was administered, 1-1.5 hours (hrs) after dose, 3-4 hrs after, 5-6 hrs after, and pre-next dose. Samples were collected on multiple days and averaged to arrive at a single value. Comparison of EBE for volume of distribution by age cohort normalized to 1kg of body weight are presented below. Sampling schedule details for PTN\_POPS & Staph Trio were comparable.
Time frame: After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).
Population: In order to determine the impact of obesity and the best weight measure for dosing, only children ≥ 2 years of age were compared (PTN\_Clinda obese study n = 21; PTN\_POPS study n = 104; and Staph Trio study n = 0). The PK model suggested dosing should be based on Total Body Weight (TBW) regardless of obesity status.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clindamycin- Ages >2 to 6 Years Old (Non-Obese) | PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 0.8 L/kg |
| Clindamycin- Ages >2 to 6 Years Old (Obese) | PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 0.9 L/kg |
| Clindamycin- Ages >6 to 12 Years Old (Non-Obese) | PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 0.9 L/kg |
| Clindamycin- Ages >6 to 12 Years Old (Obese) | PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 1.0 L/kg |
| Clindamycin- Age >12 Years Old (Non-Obese) | PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 0.9 L/kg |
| Clindamycin- Age >12 Years Old (Obese) | PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin. | 0.9 L/kg |
Post Hoc
Half-life
In order to understand the impact of obesity on clindamycin PK, PK data were combined to build a PK model from 3 studies that included both obese and non-obese children: 1) PTN\_Clinda Obese study (clinicaltrials.gov/ct.gov identifier NCT01744730) n = 21; 2) PTN\_POPS study (ct.gov identifier NCT01431326) n = 178; and 3) Staph Trio study (ct.gov identifier NCT01728363) n = 21. The data from the Staph-Trio study were only included for PK modeling and not intended to be compared in the analysis. PK sampling schedule for PTN\_Clinda Obese was: Pre-dose 0 (within 15 minutes prior to IV clindamycin dose), 0.5 (± 5 minutes) after dose was administered, 1-1.5 hours (hrs) after dose, 3-4 hrs after, 5-6 hrs after, and pre-next dose. Samples were collected on multiple days and averaged to arrive at a single value. Comparison of empirical Bayesian Estimates (EBE) for half-life by age cohort are presented below. Sampling schedule details for PTN\_POPS and Staph Trio were comparable.
Time frame: After participant transitioned from IV Clindamycin to oral Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).
Population: In order to determine the impact of obesity and the best weight measure for dosing, only children ≥ 2 years of age were compared (PTN\_Clinda obese study n = 21; PTN\_POPS study n = 104; and Staph Trio study n = 0). The PK model suggested dosing should be based on Total Body Weight (TBW) regardless of obesity status.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clindamycin- Ages >2 to 6 Years Old (Non-Obese) | Half-life | 2.4 hours |
| Clindamycin- Ages >2 to 6 Years Old (Obese) | Half-life | 2.2 hours |
| Clindamycin- Ages >6 to 12 Years Old (Non-Obese) | Half-life | 2.2 hours |
| Clindamycin- Ages >6 to 12 Years Old (Obese) | Half-life | 3.0 hours |
| Clindamycin- Age >12 Years Old (Non-Obese) | Half-life | 2.8 hours |
| Clindamycin- Age >12 Years Old (Obese) | Half-life | 3.6 hours |